1. Field of the Invention
This invention relates to novel 1,2,4-oxadiazolyl-phenoxyalkylisoxazoles, to methods for the preparation thereof, and compositions and methods for the use thereof as antiviral agents.
2. Information Disclosure Statement
Diana U.S. Pat. No. 4,843,087, issued Jun. 27, 1989, discloses heteryl-phenoxyalkylisoxazoles, wherein the heteryl moiety is an oxazole or an oxazine, which exhibit antiviral activity.
Diana et al. U.S. Pat. No. 4,857,539, issued Aug. 15, 1989, discloses antivirally active compounds of the formula ##STR2## wherein: Y is an alkylene bridge of 3-9 carbon atoms;
Z is N or HC: PA1 R is hydrogen or lower-alkyl of 1-5 carbon atoms, with the proviso that when Z is N, R is lower-alkyl; PA1 R.sub.1 and R.sub.2 are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and PA1 X is O, S, SO or SO.sub.2 ; PA1 Z is N or R.sub.8 C, where R.sub.8 is hydrogen or lower-alkanoyl; PA1 R.sub.1 and R.sub.2 are selected from the group consisting of hydrogen, lower-alkyl, lower-alkenyl, halogen, lower-alkoxy, lower-alkylthio, difluoromethyl, trifluoromethyl, amino, lower-alkanoylamino, di-lower-alkylamino, hydroxy, lower-alkenoyl, lower-alkanoyl, hydroxymethyl and carboxy; PA1 R and R.sub.3 are each hydrogen or alkyl of 1 to 3 carbon atoms optionally substituted by a member of the group consisting of hydroxy, lower-alkanoyloxy, lower-alkoxy, halo or N.dbd.Z', wherein N.dbd.Z' is amino, lower-alkanoylamino, lower-alkylamino, di-lower-alkylamino, 1 -pyrrolidyl, 1-piperidinyl or 4-morpholinyl; with the proviso that when Z is N, R is other than hydrogen; and PA1 R' is lower-alkyl or hydroxy-lower-alkyl of 1-5 carbon atoms; PA1 R.sub.1 and R.sub.2 are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and PA1 R.sub.8 is hydrogen or lower-alkyl of 1-5 carbon atoms. PA1 R' is lower-alkyl or hydroxy-lower-alkyl of 1-5 carbon atoms; PA1 R.sub.1 and R.sub.2 are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and PA1 R.sub.8 is hydrogen or lower-alkyl of 1-5 carbon atoms. PA1 R.sub.1 is lower-alkyl, lower-alkoxy-(C.sub.1-3 -alkyl), lower-alkoxycarbonyl, cyclopropyl or trifluoromethyl; PA1 R.sub.2 and R.sub.3 independently are hydrogen, lower-alkyl, halogen, lower-alkoxy, nitro, trifluoromethyl or hydroxy; and PA1 R.sub.4 is hydrogen or lower-alkyl; where lower-alkyl and lower-alkoxy, each occurrence, have from 1-5 carbon atoms; PA1 Y is alkylene of 3 to 9 carbon atoms, PA1 R.sub.2 and R.sub.3 independently are hydrogen, alkyl, alkoxy, halo, cyano, trifluoromethyl or nitro; PA1 R.sub.4 is alkoxy, hydroxy, halomethyl, dihalomethyl, trihalomethyl, dihaloethyl, cycloalkyl, heterocyclyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, alkanecarbonyloxyalkyl, cyano, halo, thioalkyl, alkylthioalkyl, alkylthio, thio, 2,2,2-trifluoroethyl, 2,2,2-trihaloethyl, (4-methylphenyl)-sulfonyloxy-methyl, N.dbd.Q or CON.dbd.Q, where N.dbd.Q is amino, alkylamino or dialkylamino; PA1 R.sub.5 is halo, or hydrogen, or alkyl.
Het is selected from specified heterocyclic groups. Included in the definition of Het is unsubstituted 1,3,4-oxadiazol-2-yl and unsubstituted 1,2,4-oxadiazol-5-yl.
Diana et al. U.S. Pat. No. 4,861,791, issued Aug. 29, 1989, discloses antivirally active compounds of the formula, inter alia, ##STR3## wherein: Y is an alkylene bridge of 3 to 9 carbon atoms optionally interrupted by one or two oxygen atoms, by cyclohexyl or by an olefinic linkage;
Het is selected from specified heterocyclic groups including unsubstituted 1,3,4-oxadiazol-2-yl.
Diana et al. U.S. Pat. No. 4,942,241, issued Jul. 17, 1990, discloses antivirally active compounds of the formulas ##STR4## wherein: Y is an alkylene bridge of 1-9 carbon atoms;
Diana U.S. Pat. No. 4,945,164, issued Jul. 31, 1990, discloses antivirally active compounds of the formula, inter alia, ##STR5## wherein: Y is an alkylene bridge of 3-9 carbon atoms;
Commonly assigned G. D. Diana and T. R. Bailey U.S. patent application Ser. No. 07/731,569, filed Jul. 17, 1991, discloses compounds of the formula ##STR6## wherein: Y is alkylene of 3 to 9 carbon atoms;
with the proviso that when R.sub.1 is lower-alkyl, at least one of R.sub.2 and R.sub.3 is hydroxy.